• Medientyp: E-Artikel
  • Titel: C/EBP Homologous Protein-10 (CHOP-10) Limits Postnatal Neovascularization Through Control of Endothelial Nitric Oxide Synthase Gene Expression
  • Beteiligte: Loinard, Céline; Zouggari, Yasmine; Rueda, Patricia; Ramkhelawon, Bhama; Cochain, Clément; Vilar, José; Récalde, Alice; Richart, Adéle; Charue, Dominique; Duriez, Micheline; Mori, Masataka; Arenzana-Seisdedos, Fernando; Lévy, Bernard I.; Heymes, Christophe; Silvestre, Jean-Sébastien
  • Erschienen: Ovid Technologies (Wolters Kluwer Health), 2012
  • Erschienen in: Circulation
  • Sprache: Englisch
  • DOI: 10.1161/circulationaha.111.041830
  • ISSN: 0009-7322; 1524-4539
  • Schlagwörter: Physiology (medical) ; Cardiology and Cardiovascular Medicine
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  • Beschreibung: <jats:sec> <jats:title>Background—</jats:title> <jats:p>C/EBP homologous protein-10 (CHOP-10) is a novel developmentally regulated nuclear protein that emerges as a critical transcriptional integrator among pathways regulating differentiation, proliferation, and survival. In the present study, we analyzed the role of CHOP-10 in postnatal neovascularization.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results—</jats:title> <jats:p> Ischemia was induced by right femoral artery ligation in wild-type and CHOP-10 <jats:sup>−/−</jats:sup> mice. In capillary structure of skeletal muscle, CHOP-10 mRNA and protein levels were upregulated by ischemia and diabetes mellitus. Angiographic score, capillary density, and foot perfusion were increased in CHOP-10 <jats:sup>−/−</jats:sup> mice compared with wild-type mice. This effect was associated with a reduction in apoptosis and an upregulation of endothelial nitric oxide synthase (eNOS) levels in ischemic legs of CHOP-10 <jats:sup>−/−</jats:sup> mice compared with wild-type mice. In agreement with these results, eNOS mRNA and protein levels were significantly upregulated in CHOP-10 short interfering RNA–transfected human endothelial cells, whereas overexpression of CHOP-10 inhibited basal transcriptional activation of the eNOS promoter. Using a chromatin immunoprecipitation assay, we also showed that CHOP-10 was bound to the eNOS promoter. Interestingly, enhanced postischemic neovascularization in CHOP-10 <jats:sup>−/−</jats:sup> mice was fully blunted in CHOP-10/eNOS double-knockout animals. Finally, we showed that induction of diabetes mellitus is associated with a marked upregulation of CHOP-10 that substantially inhibited postischemic neovascularization. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p>This study identifies CHOP-10 as an important transcription factor modulating vessel formation and maturation.</jats:p> </jats:sec>
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